Metabolic Trade-offs in Yeast are Caused by F1F0-ATP synthase.
Metabolic Trade-offs in Yeast are Caused by F1F0-ATP synthase.
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DOI：
10.1038/srep22264
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发表时间：
2016-03-01
影响因子：
4.6
通讯作者：
Nielsen J
中科院分区：
文献类型：
--
作者：
Nilsson A;Nielsen J
中间代谢为活细胞提供合成蛋白质、脂质、RNA和其他细胞成分所需的自由能和前体代谢物，并且在活物种中高度保守。然而，只有一小部分细胞蛋白质可以分配给中间代谢的酶，因此可能发生代谢权衡。有氧发酵是其中一种权衡，它发生在酵母（克拉布特里效应）和癌细胞（瓦尔堡效应）中，几十年来一直是一个科学挑战。在这里，我们表明，使用通量平衡分析结合在体外测得的酶的比活性，发酵比呼吸更有催化效率，即它产生更多的ATP每蛋白质质量。因此，向高生长速率发酵的转变是由有限的酶库提供的高ATP产生速率的结果。与半乳糖和乙醇相比，在葡萄糖上生长的细胞的催化效率也更高，这可以解释观察到的它们生长速率的差异。F1 F0-ATP合酶（复合物V）被发现在模型中对呼吸具有通量控制，由于它是进化保守的，我们预计这种权衡会发生在所有生命王国的生物体中。
Intermediary metabolism provides living cells with free energy and precursor metabolites required for synthesizing proteins, lipids, RNA and other cellular constituents, and it is highly conserved among living species. Only a fraction of cellular protein can, however, be allocated to enzymes of intermediary metabolism and consequently metabolic trade-offs may take place. One such trade-off, aerobic fermentation, occurs in both yeast (the Crabtree effect) and cancer cells (the Warburg effect) and has been a scientific challenge for decades. Here we show, using flux balance analysis combined with in vitro measured enzyme specific activities, that fermentation is more catalytically efficient than respiration, i.e. it produces more ATP per protein mass. And that the switch to fermentation at high growth rates therefore is a consequence of a high ATP production rate, provided by a limited pool of enzymes. The catalytic efficiency is also higher for cells grown on glucose compared to galactose and ethanol, which may explain the observed differences in their growth rates. The enzyme F1F0-ATP synthase (Complex V) was found to have flux control over respiration in the model, and since it is evolutionary conserved, we expect the trade-off to occur in organisms from all kingdoms of life.